反复化学物质刺激诱导的小鼠哮喘模型中的免疫因素
2009/08/11
甲苯二异氰酸酯（TDI）是已知的职业性哮喘病因，本实验在小鼠化学性哮喘模型中研究TDI反复刺激对哮喘的影响。
BALB/c小鼠在第1和7天采用TDI或vehicle（丙酮/橄榄油）刺激，在第10、13和16天，小鼠接受鼻腔滴入TDI。每次刺激后用整体容积描记箱监测通气功能（Penh）40分钟。22小时后检测对乙酰甲胆碱的反应。24小时后检测肺泡灌洗液（BAL）内的肺部炎症、TNF-α和MIP-2水平。其它检测的免疫学指标包括总IgE、耳和颈部淋巴结中的淋巴细胞亚群，以及与有或无刀豆素A共培养的淋巴结细胞上清液中的IL-4、IFN-γ和IL-13水平。
小鼠在接受1次皮肤和1次或多次鼻腔内TDI刺激后，早期通气功能和气道反应性增加。多次刺激后，肺脏炎症表现为中性粒细胞（约15％）和嗜酸性粒细胞（约4％）浸润，伴随有BAL内的MIP-2和TNF-α的增加。所有致敏小鼠耳和颈部淋巴结中B细胞、Th细胞增加，体外释放的IL-4、IFN-γ和IL-13在刀豆素A刺激后增加。皮肤致敏的小鼠总血清IgE增加。
本实验方案建立的哮喘模型与人类哮喘类似，表明单次TDI处理的哮喘模型中小鼠的反应可能是哮喘发病的较好的首要指针。
（苏楠 审校）
Vanoirbeek JA, et al. Scand J Immunol. 2009 Jul;70(1):25-33.
Immunological determinants in a mouse model of chemical-induced asthma after multiple exposures.
Vanoirbeek JA, Tarkowski M, De Vooght V, Nemery B, Hoet PH.
Katholieke Universiteit Leuven, Research Unit of Lung Toxicology, Leuven, Belgium.
In a mouse model of chemical-induced asthma, we investigated the effects of multiple challenges, using toluene diisocyanate (TDI), a known cause of occupational asthma. On days 1 and 7, BALB/c mice received TDI or vehicle (acetone/olive oil). On days 10, 13 and 16 the mice received an intranasal instillation of TDI. Ventilatory function (Penh) was monitored by whole body plethysmography for 40 min after each challenge. Reactivity to methacholine was measured 22 h later. Pulmonary inflammation, TNF-alpha and MIP-2 levels were assessed 24 h after the last challenge by broncho-alveolar lavage (BAL). Other immunological parameters included total IgE, lymphocyte sub-populations in auricular and cervical lymph nodes, and IL-4, IFN-gamma and IL-13 levels in supernatants of lymph node cells, cultured with or without concanavalin A. Early ventilatory function and airway reactivity increased in all groups that received a dermal application and one or multiple intranasal challenges of TDI. After multiple challenges, lung inflammation was characterized by neutrophils (approximately 15%), and eosinophils (approximately 4%), along with an increase in BAL MIP-2 and TNF-alpha levels. The auricular and cervical lymph node cells of all sensitized mice showed an increase in B cells, Th cells and an increased concentration of in vitro release of IL-4, IFN-gamma and IL-13 after stimulation with concanavalin A. Total serum IgE was elevated in dermally TDI-sensitized mice. This protocol including multiple challenges results in a model that resembles human asthma, indicating that responses found in the model using a single challenge could be a good first indication for the development of asthma.
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细胞外基质在哮喘患者肺和气道反应性中的作用
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有抑郁症状的儿童哮喘患者存在气道阻力增加：发生机制为“迷走神经功能失调”？
